辛伐他汀对星形胶质细胞中组织型纤溶酶原激活剂诱导的基质金属蛋白酶-9的降低作用。
Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes.
作者信息
Wang Sophia, Lee Sun-Ryung, Guo Shu-Zhen, Kim Woo Jean, Montaner Joan, Wang Xiaoying, Lo Eng H
机构信息
Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Mass 02129, USA.
出版信息
Stroke. 2006 Jul;37(7):1910-2. doi: 10.1161/01.STR.0000226923.48905.39. Epub 2006 Jun 1.
BACKGROUND AND PURPOSE
Hemorrhagic conversion after tissue plasminogen activator (tPA) stroke therapy has been linked with elevations in matrix metalloproteinase-9 (MMP-9) at the neurovascular interface. Here, we test the idea that statins may directly ameliorate tPA-induced MMP-9 dysregulation.
METHODS
Recombinant human tPA (5 microg/mL) was added to primary rat cortical astrocytes. Zymography was used to quantify MMP-9 levels in conditioned media. Effects of simvastatin or the Rho kinase inhibitor Y-27632 were assessed by pretreating cells before tPA exposure.
RESULTS
Simvastatin (1 to 10 micromol/L) significantly reduced tPA-induced MMP-9 in cortical astrocytes. This effect may be mediated via the Rho kinase pathway because tPA-induced activation of Rho signaling was suppressed by simvastatin, and tPA-induced MMP-9 levels were similarly reduced by the Rho kinase inhibitor Y-27632 (1 to 10 micromol/L).
CONCLUSIONS
Statins reduce tPA-induced MMP-9 dysregulation by inhibiting the Rho signaling pathway. Statins may ameliorate tPA-associated MMP imbalances in stroke.
背景与目的
组织型纤溶酶原激活剂（tPA）治疗卒中后的出血性转化与神经血管界面基质金属蛋白酶-9（MMP-9）水平升高有关。在此，我们验证他汀类药物可能直接改善tPA诱导的MMP-9失调这一观点。
方法
将重组人tPA（5微克/毫升）添加到原代大鼠皮质星形胶质细胞中。采用酶谱法对条件培养基中的MMP-9水平进行定量。在tPA暴露前对细胞进行预处理，评估辛伐他汀或Rho激酶抑制剂Y-27632的作用。
结果
辛伐他汀（1至10微摩尔/升）显著降低tPA诱导的皮质星形胶质细胞中的MMP-9。这种作用可能通过Rho激酶途径介导，因为辛伐他汀抑制了tPA诱导的Rho信号激活，并且Rho激酶抑制剂Y-27632（1至10微摩尔/升）同样降低了tPA诱导的MMP-9水平。
结论
他汀类药物通过抑制Rho信号通路减少tPA诱导的MMP-9失调。他汀类药物可能改善卒中中与tPA相关的MMP失衡。
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